Program Director/Principal Investigator (Last, First, Middle): Morris, James, Culvin Project Summary/Abstract Members of the class Kinetoplastea, which includes the African trypanosome Trypanosoma brucei and Leishmania spp., place a tremendous burden on human health with an estimated ~1.4 million cases of disease recorded in 2015 (World Health Organization). Glucose metabolism is critical to the success of these parasites, suggesting that inhibition of glucose uptake and sub-cellular distribution in these parasites would be effective means of control. The goal of this application is to use fluorescence-based glucose probes in live parasites to identify inhibitors of (a.) environmental glucose uptake and (b.) organellar glucose uptake. We will systematically confirm the inhibitory activity of primary hits using a series of secondary confirmation assays with hits being scored for anti-parasitic activity. Through an iterative approach that weighs activity against glucose uptake and parasite viability, scaffolds will be identified that are potent inhibitors of glucose uptake with promising broad-spectrum anti-kinetoplastid activity. PHS 398/2590 (Rev. 06/09) Page 1 Continuation Format Page